Despite the severe health consequences of smoking and the desire of most smokers to quit, tens of millions of Americans continue to smoke. This in part reflects the poor efficacy of existing smoking cessation therapies, which result in sustained abstinence in a small minority of users. While most current smoking cessation therapies deliver nicotine in an effort to alleviate cigarette craving, none delivers nicotine as quickly as cigarettes do. The goal of the current work is to develop and commercialize a nicotine replacement product that more effectively relieves cigarette craving by delivering nicotine with similar pharmacokinetics to those produced by cigarette smoking. Such rapid, pulsatile nicotine delivery would be achieved via inhalation of pure nicotine aerosols. To date, we have built a small test apparatus that produces pure nicotine aerosols in the particle size range required for rapid systemic and thus brain delivery via deep lung inhalation. In this Phase I grant, we propose to apply this technology in the design of multi-dose, handheld, breath-actuated inhalers. In grant Phase II and III, we would then test these inhalers in smokers, measuring their efficacy both in relieving acute cigarette craving and in enabling long term cigarette abstinence. Subsequent commercialization of the novel nicotine replacement therapy would provide a valuable addition to the tools available to help smokers quit, and as such could potentially save thousands of lives annually.